Abstract Sudden cardiac arrest occurring in infants and children is emotionally devastating for family members and results in quality-adjusted life-years lost that are far greater that adult sudden cardiac arrest. The absolute importance of quality cardiopulmonary resuscitation (CPR) has been re-emphasized in the most recent iteration of basic and advanced life support guidelines published by the American Heart Association (AHA) and the International Liaison Committee on Resuscitation (ILCOR). Basic life support consists of chest compressions, mouth-to-mouth ventilation (if the rescuer is trained to do so), and the use of automated external defibrillators (AEDs) if available. Advanced life support adds the acquisition of vascular access, delivery of resuscitation drugs, application of fully functional monitor/defibrillators, and the use of advanced airway devices. The new AHA/ILCOR guidelines were published in October 2015. These were developed via a rigorous and transparent evidence evaluation process, though there are instances in which the evidence is either weak or non-existent. Such is the case for pediatric chest compression rate and depth during CPR, where very few data inform the recommendations. Pediatric Chest Compression Rate: Current guidelines state, ?Compression rate was not reviewed because of insufficient evidence, and we recommend that rescuers use the adult rate? (Updated). Pediatric Chest Compression Depth: The depth recommendation was actually downgraded. ?The Class of Recommendation was downgraded from Class I to Class IIa, primarily based on the rigor of the evidence evaluation.? These point to clear knowledge gaps in the scientific evidence. Approach: Using our one-of-a-kind signal-guided chest compression device that uses physiologic feedback to adjust its chest compression parameters, we will fill in these knowledge gaps by determining the optimum chest compression depths and rates in porcine models of infant and child asphyxial cardiac arrest. Aim 1: We will compare coronary perfusion pressure (CPP) and carotid blood flow (CBF) using fixed chest compression depths to the depth determined by physiologic feedback given to the signal- guided chest compression device. Aim 2: We will compare CPP and CBF using a fixed chest compression rate (100 per minute) to the rate determined by physiologic feedback given to the signal-guided chest compression device. Aim 3: We will determine whether the optimum chest compression depth and rate for the infant-sized model differ from those of the child-sized model and thus need separate or uniform recommendations. Translational Impact: Using physiologically-guided (rather than arbitrary) parameters, this large preclinical study will provide compelling evidence in determining the optimum chest compression depth and rate for pediatric CPR and could be readily translated by informing future guidelines.